Effects of Yizhi Tiaoshen acupuncture on learning and memory function and the expression of phosphorylated tau protein in the hippocampus of Alzheimer's disease model rats / 中国针灸

OBJECTIVE@#To observe the effects of Yizhi Tiaoshen (benefiting mental health and regulating the spirit) acupuncture on learning and memory function, and the expression of phosphorylated tubulin-associated unit (tau) protein in the hippocampus of Alzheimer's disease (AD) model rats, and explore the effect mechanism of this therapy on AD.@*METHODS@#A blank group and a sham-operation group were randomly selected from 60 male SD rats, 10 rats in each one. AD models were established in the rest 40 rats by the intraperitoneal injection of D-galactose and okadaic acid in the CA1 region of the bilateral hippocampus. Thirty successfully-replicated model rats were randomly divided into a model group, a western medication group and an acupuncture group, 10 rats in each one. In the acupuncture group, acupuncture was applied to "Baihui" (GV 20), "Sishencong" (EX-HN 1), "Neiguan" (PC 6), "Shenmen" (HT 7), "Xuanzhong" (GB 39) and "Sanyinjiao" (SP 6); and the needles were retained for 10 min. Acupuncture was given once daily. One course of treatment was composed of 6 days, with the interval of 1 day; the completion of treatment included 4 courses. In the western medication group, donepezil hydrochloride solution (0.45 mg/kg) was administrated intragastrically, once daily; it took 7 days to accomplish one course of treatment and a completion of intervention was composed of 4 courses. Morris water maze (MWM) and novel object recognition test (NORT) were used to assess the learning and memory function of the rats. Using HE staining and Nissl staining, the morphological structure of the hippocampus was observed. With Western blot adopted, the protein expression of the tau, phosphorylated tau protein at Ser198 (p-tau Ser198), protein phosphatase 2A (PP2A) and glycogen synthase kinase-3β (GSK-3β) in the hippocampus was detected.@*RESULTS@#There were no statistical differences in all of the indexes between the sham-operation group and the blank group. Compared with the sham-operation group, in the model group, the MWM escape latency was prolonged (P<0.05), the crossing frequency and the quadrant stay time in original platform were shortened (P<0.05), and the NORT discrimination index (DI) was reduced (P<0.05); the hippocampal cell numbers were declined and the cells arranged irregularly, the hippocampal neuronal structure was abnormal and the numbers of Nissl bodies decreased; the protein expression of p-tau Ser198 and GSK-3βwas increased (P<0.05) and that of PP2A decreased (P<0.05). When compared with the model group, in the western medication group and the acupuncture group, the MWM escape latency was shortened (P<0.05), the crossing frequency and the quadrant stay time in original platform were increased (P<0.05), and DI got higher (P<0.05); the hippocampal cell numbers were elevated and the cells arranged regularly, the damage of hippocampal neuronal structure was attenuated and the numbers of Nissl bodies were increased; the protein expression of p-tau Ser198 and GSK-3β was reduced (P<0.05) and that of PP2A was increased (P<0.05). There were no statistically significant differences in the above indexes between the acupuncture group and the western medication group (P>0.05).@*CONCLUSION@#Acupuncture therapy of "benefiting mental health and regulating the spirit" could improve the learning and memory function and alleviate neuronal injure of AD model rats. The effect mechanism of this therapy may be related to the down-regulation of GSK-3β and the up-regulation of PP2A in the hippocampus, and then to inducing the inhibition of tau protein phosphorylation.

Encefalopatía traumática crónica, definición, diagnóstico y prevención: revisión de la literatura / Chronic traumatic encephalopathy, definition, diagnosis and prevention: review of literature

La encefalopatía traumática crónica (ETC) es una enfermedad neurodegenerativa que se produce como consecuencia traumatismos cerebrales repetitivos; concusiones, que son un síndrome clínico que se caracteriza por una alteración de la función cerebral. Una concusión, bajo su estricta definición, no debiese causar cambios estructurales en el cerebro por lo que no sería visible a través de imágenes, sí existen cambios a nivel microscópicos, bioquímicos y biomecánicos. La mayoría de los pacientes tienen completa resolución de sus síntomas dentro de 10 días (90 por ciento), pero existe un pequeño porcentaje que persiste con estos, pudiendo presentarse como un síndrome postconcusional, síndrome de segundo impacto o una encefalopatía traumática crónica. La ETC se caracteriza por la acumulación de prot-tau hiperfosforilada en neuronas y astrocitos. Estas se van a presentar en forma de ovillos o hilos neurofibrilares. En etapas iniciales las encontraremos de forma focalizada en la corteza frontal y en las formas más severas su distribución será más generalizada, distribuyéndose en la mayoría de las regiones del cerebro. Su diagnóstico se realiza a través de histopatología, por lo que hasta el momento sólo se ha logrado post-mortem. Se está trabajando en nuevas tecnologías asociadas a biomarcadores y PET para lograr una diagnostico premortem. El mayor énfasis en el manejo de esta taupatía es la prevención y adecuado manejo de las concusiones.

Chronic Traumatic Encephalopathy (CTE) is a neurodegenerative disease which is produced as a consequence of repeated brain trauma: concussions, which are a clinical syndrome characterized by an alteration in brain functions. A concussion, understrict definition, should not cause structural changes to the brain. Therefore, it would not be possible to see through images if there were changes at a microscopic, biochemical level. Most patients see their symptoms completely resolved within 10 days (90 percent), but there is a small percentage which persists, and these might cause a post-concussional syndrome, second impact syndrome of chronic traumatic encephalopathy. CTE is characterized by the accumulation of hyper-phosphorylated Tau protein in neurons and astrocytes. These appear in the form of neurofibrillary tangles. During the initial stages they are focalized in the frontal cortex and, in more severe cases, their distribution is more generalized, spreading through the majority of the regions in the brain. It is diagnosis is done through histopathology. Thus, it has only been possible to do post mortem. New technologies associated with bio-markers and PET are being worked on to achieve a pre-mortem diagnosis. The greatest emphasis in the handling of this tauopathy lies in the prevention and the adequate handling of concussions.

Study of two kinds of Alzheimer's disease tree shrew models / 中国药理学通报

Aim To explore the optimized tree shrews model of Alzheimer's disease through comparison of the pathology changes of brain neurons between the two kinds of tree shrew models.Methods Fifty tree shrews were randomly divided into five groups with 10 in each group:control group,high dose D-galactose combined with ibotenic acid (IBO) group,low dose D-galactose combined with IBO group [intraperitoneal injection D-galactose combined with IBO injection into bilateral basal nucleus of Meynert (BNM)],high dose Aβ25-35 combined with IBO group,and low dose Aβ25-35 combined with IBO group (injection into bilateral BNM).Hematoxylin and eosin (HE) staining was used to observe the morphological changes of brain neurons.The expressions of choline acetyltransterase (ChAT) and synaptophysin(SYP) in the brains were detected by immunohistochemical staining.Western blot was used to detect the expression of amyloid beta 1-42 (Aβ1-42),amyloid precursor protein (APP) and phosphorylated tau protein (p-tau).Results The HE staining showed there were different degrees of morphological changes in the brains of model groups.The changes in the high dose D-galactose and high dose Aβ25-35 combined with IBO group were more obvious than those in low dose D-galactose and Aβ25-35 combined with IBO group.Immunohistochemical staining revealed that the levels of ChAT and SYP in the model groups decreased compared with control group,and the decline in high dose Aβ25-35 combined with IBO group was more marked than that in low dose Aβ25-35 combined with IBO group(P ＜0.01).Western blot revealed that the levels of Aβ1-42,APP,p-tau in the model groups increased compared with control group,and the rise in high dose Aβ25-35 combined with IBO group was more apparent than that in low dose Aβ25-35 combined with IBO group (P ＜ 0.05 or P ＜ 0.01).Conclusion The method of modeling by Aβ25-35 combined with IBO injection into bilateral BNM is more suitable for the establishment of Alzheimer's disease model.

Effect of controlled low threshold blood pressure on the expression of A β42 and p-Tau-181 protein in cerebrospinal fluid and cognition after operation in aged rats / 实用医学杂志

Objective To investigate the effects of different duration hypotension thresholds on p-Tau-181 and Aβ-42 protein expression and cognition in rats. Methods Thirty-nine healthy male SD rats were randomly di-vided into 4 groups:the control group(group C,n=9),the hypotension group(groupA1、A2、A3 ,n=10). The blood pressure of groupA1、A2、A3 was measured in different time of 2 h、4 h、6 h ,for 5 days. The antihyperten-sive group of mean arterial pressure(MAP)were maintained in the 50~55 mmHg safe range. Morris water maze was used to detect the spatial learning and memory ability of rats. The levels of Aβ42 and p-Tau-181 were detected by ELISA. Results There was no significant difference in mortality of rats in each group (P > 0.05). Compared with the group C,the escape latency and swimming distance of A2 group and A3 group were increased(P<0.05). In 3~7 days after operation,the cerebrospinal fluid P-Tau-181 and Aβ42 protein expression increased in the A2 group and A3 group compared with the A1 group(P<0.05). The escape latency and swimming distance of the A2 group and the A3 group were significantly longer than those in the control group. Aβ42 and p-Tau-181 were signifi-cantly increased in A3 group(P < 0.05). Compared with the A2 group,the increase of Aβ42 and p-Tau-181 in the A3 group was not significant(P<0.05). Conclusion Long-term controlled hypotension may lead to postoper-ative cognitive dysfunction which may relate to the increase of Aβ42 and p-Tau-181 protein expression.

Effects of neonatal repeated intermittent inhalation of sevoflurane on learning-memory and Tau protein, p-Tau protein in juvenile and adult rats / 医学研究生学报

Objective Learning and memory function is the form of brain higher nervous activity .Hippocampus is the main parts responsible for learning and memory function .Once damaged , it will seriously affect the quality of life in patients .The purpose of this paper was to observe the effects of neonatal repeated intermittent sevoflurane inhalation on learning-memory function and Tau protein , p-Tau protein in brain hippocampus in juvenile and adult rats . Methods Twenty-four healthy SD rats ( n=24 ) were randomly di-vided into juvenile sevoflurane inhalation group ( n=6) , juvenile con-trol group ( n=6);adult sevoflurane inhalation group ( n=6) , and adult control group ( n=6) .Rats in juvenile sevoflurane inhalation group and adult sevoflurane inhalation group inhaled 2.6%sevoflurane at the postnatal 7th day, 14th day, 21th day ( P7,P14,P21) for 2 hours.Rats in juvenile control group and adult control group inhaled the carrier gas (1L/min Air+1L/min O2) at the same time for 2 hours.During P31~37, Morris water maze test was conducted in juvenile sevoflurane inhalation group and juvenile control group to detect the behavior.During P91~97, Morris water maze test was conducted in adult sevoflurane inhalation group and adult control group to detect the behavior .Then hippocampi were taken out to detect the expression levels of Tau protein and p -Tau protein. Results ( 1) Comparison of escape latency at the same time ① Juvenile period: no statistical difference between sevoflurane inhalation group (52.04±41.90,29.77±14.23, 19.87±5.71,22.74±13.73,21.91±9.07) and control group (47.82±8.06,25.26±12.53,23.79±9.49, 20.00±10.10, 14.03±7.55) had (P>0.05).② Adult period: no statistical difference between sevoflurane inhalation group (42.00± 14.12, 26.87±16.93, 19.80±13.76, 15.06±8.45, 8.66±4.82) and control group (41.97±25.66,22.88±10.04,15.88±5.20,9.26± 3.98,11.33±6.05 (P>0.05).(2) Comparison of spatial probe test results:no statistical difference in the swimming times from original area,swimmingresidencetime,swimmingdistanceandspeedbetweengroups(P>0.05).(3)Tauproteinexpressiondetection ①Juvenile period:In the hippocampal CA1 region, CA3 region, DG region, the expression level of Tau in the sevoflurane inhalation group (0.237±0.015, 0.324±0.024,0.226±0.019) was higher than the control group (0.185±0.024,0.232±0.040, 0.184±0.018) (P>0.01).②Adult peroid:no statistically significant difference between sevoflurane inhalation group and control group (P>0.05). (4)p-Tau(Ser396)proteinexpressiondetection ①Juvenileperiod:nostatisticallysignificantdifferencebetweensevofluraneinhala-tion group and control group ( P>0.05) .②Adult period:The expression level in the hippocampal CA3 region of sevoflurane inhalation group (0.170±0.005) was higher than control group (0.158±0.011) (P0.05). Conclusion Neonatal repeated intermittent sevoflurane inhalation has done no harm to learn-ing and memory function of juvenile and adult rats , however , it can result in the significant increase of hippocampal Tau protein expres-sion level in juvenile rats and the increase of hippocampal p-Tau protein expression level in adult rats .

Significance and detection of Aβ42 and P-tau levels in CSF of patients with mild cognitive impairment / 实用医学杂志

Objective To investigate Aβ42 and P-tau levels in cerebrospinal fluid (CSF) of patients with mild cognitive impairment (MCI). Methods CSF of 25 cases of MCI and 14 cases of cognitively normal (CN) were investigated. The CSF levels of Aβ42 and P-tau were detected by ELISA method. Correlation analysis was used to analyze the correlation between P-tau level and MMSE score in MCI. Results The CSF level of Aβ 42 was higher and P-tau was lower in MCI than CN group(P<0.05). P-tau level in MCI was also negatively correlated with MMSE score (P<0.05). Conclusion Aβ42 and P-tau levels in CSF may be valuable biological markers in the diagnosis of MCI. P-tau level in CSF of MCI may be related to the severity of cognitive impairment.